Ultrasound-triggered reactive oxygen species effector nanoamplifier for enhanced combination therapy of mutant p53 tumors

Xiang Wang; Kang Song; Yan Fan; Jun Du; Jinliang Liu; Jiayu Xu; Lulu Zheng; Ruizhuo Ouyang; Yuhao Li; Yuqing Miao; Dawei Zhang

doi:10.1016/j.colsurfb.2022.112489

Ultrasound-triggered reactive oxygen species effector nanoamplifier for enhanced combination therapy of mutant p53 tumors

Colloids Surf B Biointerfaces. 2022 Jul:215:112489. doi: 10.1016/j.colsurfb.2022.112489. Epub 2022 Apr 4.

Authors

Xiang Wang¹, Kang Song¹, Yan Fan², Jun Du¹, Jinliang Liu¹, Jiayu Xu¹, Lulu Zheng², Ruizhuo Ouyang³, Yuhao Li⁴, Yuqing Miao³, Dawei Zhang²

Affiliations

¹ Institute of Bismuth and Rhenium Science & School of Materials and Chemistry, University of Shanghai for Science and Technology, Shanghai 200093, China.
² Engineering Research Center of Optical Instrument and System, the Ministry of Education, Shanghai Key Laboratory of Modern Optical System, University of Shanghai for Science and Technology, Shanghai 200093, China.
³ Institute of Bismuth and Rhenium Science & School of Materials and Chemistry, University of Shanghai for Science and Technology, Shanghai 200093, China; Shanghai Collaborative Innovation Center of Energy Therapy for Tumors, University of Shanghai for Science and Technology, Shanghai 200093, China.
⁴ Institute of Bismuth and Rhenium Science & School of Materials and Chemistry, University of Shanghai for Science and Technology, Shanghai 200093, China; Shanghai Collaborative Innovation Center of Energy Therapy for Tumors, University of Shanghai for Science and Technology, Shanghai 200093, China. Electronic address: yhli@usst.edu.cn.

PMID: 35395477
DOI: 10.1016/j.colsurfb.2022.112489

Abstract

Reactive oxygen species (ROS) damage is a crucial method with which to inhibit tumor cell proliferation; however, tumor cells can reduce ROS damage by modulating multiple repair mechanisms, thus, reducing the efficacy of ROS damage in tumor therapy. In this study, we built an ultrasound-triggered ROS damage nanoamplifier using a synergistic strategy consisting of ROS damage and decreased tumor self-protection capability to enhance the treatment efficacy of mutant p53 tumors. A ROS damage nanoamplifier (PT@PTGA) was fabricated using amphiphilic polyglutamic acid (PTGA) to load with a sonosensitizer (protoporphyrin IX, PpIX) and an MTH1 inhibitor (TH287). Under ultrasonic excitation, PpIX catalyzes oxygen to produce singlet oxygen and release TH287 to inhibit MTH1 activity, thereby causing the accumulation of 8-oxo-dGTP, which enhances DNA damage and further induces cell apoptosis. In addition, TH287 allies with ROS to eliminate the mutated p53 protein in tumor cells, thus reducing the self-protective capacity of tumor cells. As a result, the "internal and external" aspects were combined to enhance sensitization for mutant p53 tumor therapy. The construction of a ROS nanoamplifier not only provides an effective strategy for the treatment of mutant p53 tumors but also supplies an integrated platform for tumor diagnosis and therapy.

Keywords: Amphiphilic polyglutamic acid; Mutant p53 protein; ROS damage; Sonodynamic therapy; Synergistic therapy.

MeSH terms

Apoptosis
Cell Line, Tumor
Cell Proliferation
Humans
Neoplasms* / drug therapy
Neoplasms* / genetics
Reactive Oxygen Species / metabolism
Tumor Suppressor Protein p53* / genetics
Tumor Suppressor Protein p53* / pharmacology

Substances

Reactive Oxygen Species
Tumor Suppressor Protein p53